基于lncRNA-PRINS调控G1P3/microRNA-491-5p探讨麻防犀角地黄汤治疗银屑病的机制

Psoriasis is one of the most important skin diseases which affecting human health, but there is no cure for it. The pathogenesis of the disease involves inflammatory micro-environment and hyperproliferation of the keratinocytes(KC), and hyperproliferation of lncRNA-PRINS is one of the mechanisms contributing to the disease. The previous study found that Ma-Fang-Xi-jiao-Di-Huang Decoction had obvious therapeutic effect on psoriasis, but the mechanism is not clear. In the current proposal, we will investigate the role of lncRNA-PRINS in hyperproliferation and inflammatory signal of KC and the mechanism of Ma-Fang-Xi-jiao-Di-Huang Decoction by constructing lncRNA-PRINS overexpression and defective plasmid and the medicated serum. Then, C57BL/6 mice psoriasis model induced by propranolol/imiquimod were used to reveal the hypothesis that Ma-Fang-Xi-jiao-Di-Huang Decoction regulates lncRNA-PRINS expression, alleviates inflammation, controls hyperproliferation of KC and delays psoriasis progression. The study will provide scientific clues in clinical use in treating Psoriasis for traditional Chinese medicine.

银屑病（Psoriasis）是影响人类健康的最主要的皮肤疾患之一，但目前尚无根治办法，其发病机制涉及炎症微环境和角质形成细胞（KC）异常增殖等多种环节，其中lncRNA-PRINS参与的炎症信号和KC异常增殖起着重要作用。课题组前期研究发现，麻防犀角地黄汤对于银屑病具有明显的治疗效果，但具体机制尚不清楚。因此，本课题拟构建lncRNA-PRINS过表达和缺陷质粒及麻防犀角地黄汤含药血清共培养的KC模型；并通过构建普萘洛尔/咪喹莫特诱导的C57BL/6银屑病小鼠及麻防犀角地黄汤干预模型，采用相关技术检测lncRNA-PRINS、KC异常增殖中G1P3和microRNA-491-5p/PI3K/AKT/mTOR炎症信号的表达，阐释麻防犀角地黄汤通过调控lncRNA-PRINS表达，减轻炎症并控制KC异常增殖，延缓银屑病进展的科学假说，为中医药治疗银屑病提供科学依据。

银屑病的发病机制涉及炎症微环境和角质形成细胞异常增殖等多种环节，lncRNA-PRINS在这些过程中发挥重要作用。LncRNA-PRINS不仅可以调控G1P3和microRNA-491-5p的表达水平，网站预测显示其与microRNA-215-5p之间也存在结合位点。课题组前期研究发现，麻防犀角地黄汤对于银屑病具有明显的治疗效果，但具体机制尚不清楚。因此，本课题构建了lncRNA-PRINS过表达和缺陷质粒，并与麻防犀角地黄汤含药血清共培养HaCaT细胞；通过咪喹莫特诱导BALB/c小鼠构建银屑病小鼠模型，给予麻防犀角地黄汤进行干预。采用相关技术检测lncRNA-PRINS、G1P3、microRNA-491-5p及PI3K/AKT/mTOR、EGFR、NF-κB/MAPK信号通路相关基因的表达水平。.研究显示，过表达lncRNA-PRINS能够上调G1P3的表达并促进角质形成细胞增殖。麻防犀角地黄汤则下调lncRNA-PRINS和G1P3的表达水平参与调节角质形成细胞增殖过程。同时，lncRNA-PRINS可负调控microRNA-491-5p的表达进而激活PI3K/AKT/mTOR信号通路。麻防犀角地黄汤通过lncRNA-PRINS/microRNA-491-5p/PI3K/AKT/mTOR信号轴对银屑病起到治疗作用。microRNA-215-5p分别在lncRNA-PRINS和DYRK1A mRNA的3'UTR区域有结合位点，即说明lncRNA-PRINS可能作为海绵吸附microRNA-215-5p调控DYRK1A的表达，麻防犀角地黄汤则同样被证明可以增加microRNA-215-5p的表达，通过DYRK1A调控EGFR信号通路，进而抑制银屑病的炎症反应。除上述机制外，麻防犀角地黄汤还可使NF-κB/MAPK信号通路失活调节银屑病的炎症反应。.综上所述，麻防犀角地黄汤可通过多种途径起到缓解银屑病的治疗作用，包括通过lncRNA-PRINS调控G1P3介导的细胞增殖；调控microRNA-491-5p轴激活PI3K/AKT/mTOR或调控microRNA-215-5p/DYRK1A轴抑制EGFR，或直接通过NF-κB/MAPK等途径缓解银屑病样炎症。该项目结果不仅为麻防犀角地黄汤的应用提供了理论依据，还为新药研发提供了参考，对治疗银屑病具有较重要的科学意义。